Photodynamic anti-tumor activity of a new chlorin-based photosensitizer against Lewis Lung Carcinoma cells in vitro and in vivo

초록

A biological significance of photodynamic therapy (PDT) with a new porphyrin derivative, DH-I-180-3 (Max. Abs. 666 nm), was examined. Experimental PDT with DH-I-180-3 against Lewis Lung Carcinoma 1 (LLC1) cells was designed in vitro and in vivo. For the comparison, PDT with an established photosensitizer, Photofrin®, was done. When the cells were treated with DH-I-180-3 (1.0 μg/ml) in vitro, the cells became fatally susceptible to the light (1.2 J/cm2) as early as in 1 h. All of these cells were irreversibly damaged in 24 h after light irradiation and categorized as necrosis. These were not seen in cells treated with Photofrin® for more than 4 h and remained unharmed by the light until the end of experiments. Mice (C57BL/6J) bearing LLC1 tumor were treated (intravenously) with DH-I-180-3 (400 to 800 μg/kg) or with Photofrin® (2 mg/kg) for 4 h. Following the light irradiation (1.2 J/cm2), retarded tumor growth was significant in mice treated with DH-I-180-3 compared with those treated with Photofrin®/PDT. Survival of mice receiving DH-I-180-3/PDT was prolonged approximately 30% and 40% compared with that of mice in a Photofrin® group. In conclusion, DHI-180-3 absorbs a longer light wavelength, and instantaneously accumulates in tumor cells to make them susceptible to the light. In mice, a significantly low dose of DH-I-180-3 as little as 400 μg/kg was sufficient to produce a successful PDT result. Thus, we conclude that DH-I-180-3 is an effective photosensitizer to be developed. Copyright © 2003 Society of Porphyrins & Phthalocyanines.

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